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. 1994 Dec;102(Suppl 10):53–56. doi: 10.1289/ehp.94102s1053

Activation of the respiratory burst oxidase.

B M Babior 1
PMCID: PMC1566992  PMID: 7705306

Abstract

The respiratory burst oxidase of phagocytes and B lymphocytes catalyzes the reduction of oxygen by NADPH to form O2-, the precursor of a group of reactive oxidants that are employed by phagocytes as microbicidal agents. The enzyme is active in stimulated cells but dominant in resting cells. It molecular weight guanine nucleotide-binding protein. The components p22phox and gp91phox from cytochrome b558, a flavohemoprotein that resides in the cortical cytoskeleton and in the membranes of the specific granules. The other components are found in the cytosol of resting cells, but migrate to the cortical cytoskeleton when the neutrophils are activated, where they assemble the active oxidase. Migration to the cortical cytoskeleton is caused in part by the appearance of a membrane binding site on one or more of the cytosolic subunits, possibly due to the phosphorylation of p47phox that takes place during cell activation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo A., Pick E., Hall A., Totty N., Teahan C. G., Segal A. W. Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature. 1991 Oct 17;353(6345):668–670. doi: 10.1038/353668a0. [DOI] [PubMed] [Google Scholar]
  2. Babior B. M. The respiratory burst oxidase. Adv Enzymol Relat Areas Mol Biol. 1992;65:49–95. doi: 10.1002/9780470123119.ch2. [DOI] [PubMed] [Google Scholar]
  3. Cross A. R., Jones O. T., Garcia R., Segal A. W. The association of FAD with the cytochrome b-245 of human neutrophils. Biochem J. 1982 Dec 15;208(3):759–763. doi: 10.1042/bj2080759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Datta R., Taneja N., Sukhatme V. P., Qureshi S. A., Weichselbaum R., Kufe D. W. Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2419–2422. doi: 10.1073/pnas.90.6.2419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinauer M. C., Orkin S. H., Brown R., Jesaitis A. J., Parkos C. A. The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complex. 1987 Jun 25-Jul 1Nature. 327(6124):717–720. doi: 10.1038/327717a0. [DOI] [PubMed] [Google Scholar]
  6. Dinauer M. C., Pierce E. A., Bruns G. A., Curnutte J. T., Orkin S. H. Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. J Clin Invest. 1990 Nov;86(5):1729–1737. doi: 10.1172/JCI114898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eklund E. A., Marshall M., Gibbs J. B., Crean C. D., Gabig T. G. Resolution of a low molecular weight G protein in neutrophil cytosol required for NADPH oxidase activation and reconstitution by recombinant Krev-1 protein. J Biol Chem. 1991 Jul 25;266(21):13964–13970. [PubMed] [Google Scholar]
  8. Green M. R., Hill H. A., Okolow-Zubkowska M. J., Segal A. W. The production of hydroxyl and superoxide radicals by stimulated human neutrophils- measurements by EPR spectroscopy. FEBS Lett. 1979 Apr 1;100(1):23–26. doi: 10.1016/0014-5793(79)81123-0. [DOI] [PubMed] [Google Scholar]
  9. HATTORI H. Studies on the labile, stable Nadi oxidase and peroxidase staining reactions in the isolated particles of horse granulocyte. Nagoya J Med Sci. 1961 May;23:362–378. [PubMed] [Google Scholar]
  10. Hayakawa T., Suzuki K., Suzuki S., Andrews P. C., Babior B. M. A possible role for protein phosphorylation in the activation of the respiratory burst in human neutrophils. Evidence from studies with cells from patients with chronic granulomatous disease. J Biol Chem. 1986 Jul 15;261(20):9109–9115. [PubMed] [Google Scholar]
  11. Hayashi T., Ueno Y., Okamoto T. Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. J Biol Chem. 1993 May 25;268(15):11380–11388. [PubMed] [Google Scholar]
  12. Hurst J. K., Loehr T. M., Curnutte J. T., Rosen H. Resonance Raman and electron paramagnetic resonance structural investigations of neutrophil cytochrome b558. J Biol Chem. 1991 Jan 25;266(3):1627–1634. [PubMed] [Google Scholar]
  13. Kanofsky J. R., Hoogland H., Wever R., Weiss S. J. Singlet oxygen production by human eosinophils. J Biol Chem. 1988 Jul 15;263(20):9692–9696. [PubMed] [Google Scholar]
  14. Knaus U. G., Heyworth P. G., Evans T., Curnutte J. T., Bokoch G. M. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991 Dec 6;254(5037):1512–1515. doi: 10.1126/science.1660188. [DOI] [PubMed] [Google Scholar]
  15. Nauseef W. M., Volpp B. D., McCormick S., Leidal K. G., Clark R. A. Assembly of the neutrophil respiratory burst oxidase. Protein kinase C promotes cytoskeletal and membrane association of cytosolic oxidase components. J Biol Chem. 1991 Mar 25;266(9):5911–5917. [PubMed] [Google Scholar]
  16. Okamura N., Curnutte J. T., Roberts R. L., Babior B. M. Relationship of protein phosphorylation to the activation of the respiratory burst in human neutrophils. Defects in the phosphorylation of a group of closely related 48-kDa proteins in two forms of chronic granulomatous disease. J Biol Chem. 1988 May 15;263(14):6777–6782. [PubMed] [Google Scholar]
  17. Okamura N., Malawista S. E., Roberts R. L., Rosen H., Ochs H. D., Babior B. M., Curnutte J. T. Phosphorylation of the oxidase-related 48K phosphoprotein family in the unusual autosomal cytochrome-negative and X-linked cytochrome-positive types of chronic granulomatous disease. Blood. 1988 Aug;72(2):811–816. [PubMed] [Google Scholar]
  18. Park J. W., Ma M., Ruedi J. M., Smith R. M., Babior B. M. The cytosolic components of the respiratory burst oxidase exist as a M(r) approximately 240,000 complex that acquires a membrane-binding site during activation of the oxidase in a cell-free system. J Biol Chem. 1992 Aug 25;267(24):17327–17332. [PubMed] [Google Scholar]
  19. Parkos C. A., Allen R. A., Cochrane C. G., Jesaitis A. J. Purified cytochrome b from human granulocyte plasma membrane is comprised of two polypeptides with relative molecular weights of 91,000 and 22,000. J Clin Invest. 1987 Sep;80(3):732–742. doi: 10.1172/JCI113128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parkos C. A., Dinauer M. C., Walker L. E., Allen R. A., Jesaitis A. J., Orkin S. H. Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Proc Natl Acad Sci U S A. 1988 May;85(10):3319–3323. doi: 10.1073/pnas.85.10.3319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Quinn M. T., Parkos C. A., Jesaitis A. J. The lateral organization of components of the membrane skeleton and superoxide generation in the plasma membrane of stimulated human neutrophils. Biochim Biophys Acta. 1989 Dec 11;987(1):83–94. doi: 10.1016/0005-2736(89)90458-6. [DOI] [PubMed] [Google Scholar]
  22. Quinn M. T., Parkos C. A., Walker L., Orkin S. H., Dinauer M. C., Jesaitis A. J. Association of a Ras-related protein with cytochrome b of human neutrophils. Nature. 1989 Nov 9;342(6246):198–200. doi: 10.1038/342198a0. [DOI] [PubMed] [Google Scholar]
  23. Ren R., Mayer B. J., Cicchetti P., Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993 Feb 19;259(5098):1157–1161. doi: 10.1126/science.8438166. [DOI] [PubMed] [Google Scholar]
  24. Rosen H., Klebanoff S. J. Hydroxyl radical generation by polymorphonuclear leukocytes measured by electron spin resonance spectroscopy. J Clin Invest. 1979 Dec;64(6):1725–1729. doi: 10.1172/JCI109637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rotrosen D., Kleinberg M. E., Nunoi H., Leto T., Gallin J. I., Malech H. L. Evidence for a functional cytoplasmic domain of phagocyte oxidase cytochrome b558. J Biol Chem. 1990 May 25;265(15):8745–8750. [PubMed] [Google Scholar]
  26. Rotrosen D., Leto T. L. Phosphorylation of neutrophil 47-kDa cytosolic oxidase factor. Translocation to membrane is associated with distinct phosphorylation events. J Biol Chem. 1990 Nov 15;265(32):19910–19915. [PubMed] [Google Scholar]
  27. Rotrosen D., Yeung C. L., Leto T. L., Malech H. L., Kwong C. H. Cytochrome b558: the flavin-binding component of the phagocyte NADPH oxidase. Science. 1992 Jun 5;256(5062):1459–1462. doi: 10.1126/science.1318579. [DOI] [PubMed] [Google Scholar]
  28. Segal A. W., Cross A. R., Garcia R. C., Borregaard N., Valerius N. H., Soothill J. F., Jones O. T. Absence of cytochrome b-245 in chronic granulomatous disease. A multicenter European evaluation of its incidence and relevance. N Engl J Med. 1983 Feb 3;308(5):245–251. doi: 10.1056/NEJM198302033080503. [DOI] [PubMed] [Google Scholar]
  29. Segal A. W., Jones O. T., Webster D., Allison A. C. Absence of a newly described cytochrome b from neutrophils of patients with chronic granulomatous disease. Lancet. 1978 Aug 26;2(8087):446–449. doi: 10.1016/s0140-6736(78)91445-9. [DOI] [PubMed] [Google Scholar]
  30. Segal A. W., West I., Wientjes F., Nugent J. H., Chavan A. J., Haley B., Garcia R. C., Rosen H., Scrace G. Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes. Biochem J. 1992 Jun 15;284(Pt 3):781–788. doi: 10.1042/bj2840781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shinagawa Y., Tanaka C., Teraoka A., Shinagawa Y. A new cytochrome in neurophilic granules of rabbit leucocyte. J Biochem. 1966 Jun;59(6):622–624. doi: 10.1093/oxfordjournals.jbchem.a128352. [DOI] [PubMed] [Google Scholar]
  32. Steinbeck M. J., Khan A. U., Karnovsky M. J. Extracellular production of singlet oxygen by stimulated macrophages quantified using 9,10-diphenylanthracene and perylene in a polystyrene film. J Biol Chem. 1993 Jul 25;268(21):15649–15654. [PubMed] [Google Scholar]
  33. Steinbeck M. J., Khan A. U., Karnovsky M. J. Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap. J Biol Chem. 1992 Jul 5;267(19):13425–13433. [PubMed] [Google Scholar]
  34. Thomas E. L., Fishman M. Oxidation of chloride and thiocyanate by isolated leukocytes. J Biol Chem. 1986 Jul 25;261(21):9694–9702. [PubMed] [Google Scholar]
  35. Thomas E. L., Jefferson M. M., Grisham M. B. Myeloperoxidase-catalyzed incorporation of amines into proteins: role of hypochlorous acid and dichloramines. Biochemistry. 1982 Nov 23;21(24):6299–6308. doi: 10.1021/bi00267a040. [DOI] [PubMed] [Google Scholar]
  36. Weiss S. J., Test S. T., Eckmann C. M., Roos D., Regiani S. Brominating oxidants generated by human eosinophils. Science. 1986 Oct 10;234(4773):200–203. doi: 10.1126/science.3018933. [DOI] [PubMed] [Google Scholar]

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